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I have had a request from one of our faculty members for references
to be
used to support the global patient instruction, "take this medication with
a full glass of water".
I can think of a variety of reasons why oral dose form medications
might
work better when taken with a full glass of water, however I haven't found
specific references which document a "global" advantage.
Some of the reasons that come to mind are:
1. A glass of water will flush the drug into the small intestine where
absorption will be accelerated.
2. Sulfonamides are less likely to produce crystallurea.
3. NSAID's and other irritant drugs will produce less GI irritation.
4. There will be more fluid in the stomach-intestine to help
dissolve the
medications.
5. Diluting the stomach acidity may protect acid labile drugs.
Does anyone know where the literature on this topic is?
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This might not be in "the literature" but if I don't use a "full glass
of water" I find that, if I don't use water, sometimes tablets (capsules, too)
get stuck in the back of my throat and as they dissolve I might start to cough
because of the irritation. And they taste bad, too! A glass of water gets
them
down into the stomach where they belong.
Hope this helps.
Rick Traub
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[Two replies - db]
From: Stephen Duffull
To: "'PharmPK.at.pharm.cpb.uokhsc.edu'"
Subject: RE: PharmPK Re: Take with a full glass of water...
Date: Thu, 9 Jul 1998 16:35:04 +0100
MIME-Version: 1.0
Hi Vahn and Rick
I think the purpose of recommended that drugs are taken with a glass of
water is mostly to avoid the risk of oesophagitis. There is a relatively
large body of literature on drug induced oesophagitis (I found over 200
articles on MEDLINE alone). Some drugs are more likely to cause this than
others (eg tetracyclines are a well documented cause) and capsule
formulations are often worse than tablets (due to their "stickyness" when
wet).
Regards
Steve
=======================
Stephen Duffull
School of Pharmacy
University of Manchester
M13 9PL, UK
Ph +44 161 275 2355
Fax +44 161 275 2396
Email: sduffull.at.fs1.pa.man.ac.uk
---
From: ahmadmir.aaa.nrcgeb.ac.ir (Ahmad Mirfazaelian)
Subject: Re: PharmPK Take with a full glass of water...
To: PharmPK.at.pharm.cpb.uokhsc.edu
Date: Thu, 9 Jul 1998 22:03:09 -0400 (EDT)
Mime-Version: 1.0
Dear Vahn,
What i have always thought of 'full glass of ...' is that it might just
be for standardization. For all human experiment we use this amount &
just in this case our results can be extrapolated to the patients.
Ahmad
A. Mirfazaelian Pharm.D.
Dept. of Pharmaceutical Sciences
College of Pharmacy
Teheran Univ. Med. Sci.
Teheran,Iran
Phone: (+98)-021-6026452,844162
Fax: (+98)-021-6419539
e.mail: ahmadmir.-a-.nrcgeb.ac.ir
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[A few of replies - db]
Date: Fri, 10 Jul 1998 11:31:13 -0400 (EDT)
From: Chris Town
To: PharmPK.at.pharm.cpb.uokhsc.edu
Subject: Re: PharmPK Take with a full glass of water...
My son had difficulty taking tetracycline when he took it without water. The
capsule stuck in his esophagus for some period of tme and caused a serious
irritation. His pediatrician indicated that the discomfort that he felt is
often reported by individuals taking tetracycline without water. I hope
this sheds further light on the need for water.
Chris Town
---
Reply-To: "David H. Ellis" <.at.erinet.com>
From: "David H. Ellis"
To:
Subject: Full glass of water
Date: Fri, 10 Jul 1998 20:57:05 -0400
MIME-Version: 1.0
X-Priority: 3
One variable in drug PK is due to disolution, is it not? If you take a drug
on an empty stomach and its solubility is low, you must await build up of
saliva, stomach fluids, etc for the fluid volume to reach that critical
(solubility) level. If you take the drug with a full glass of water, you're
bound to solubilize the drug right away, eh? I'm new to this game... I'm a
toxicologist by training, so if this is not correct please correct me.
Dave
David H. Ellis
dhellis.-at-.erinet.com
---
X-Sender: rjmeyer.aaa.globaldialog.com
Date: Fri, 10 Jul 1998 23:20:39 -0500
To: PharmPK.-a-.pharm.cpb.uokhsc.edu
From: Bob Meyer
Subject: Re: PharmPK Re: Take with a full glass of water...
Mime-Version: 1.0
I'd agree that this is probably the primary reason for drinking the full
glass of water. Another reason, I think, is to mimic as closely as
possible the conditions under which the dissolution studies are done. This
should aid in achieving a reproducable rate of release of the drug from
it's dosage form and allow for a somewhat predictable rate of absorption.
Bob Meyer, RPh
rjmeyer.-at-.globaldialog.com
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The effect of water volume on bioavailability has been discussed by Welling
(1980) in Progress in Drug Metabolism, Vol. 4 Chap. 3. He shows what
appears to be a substantial increase in absorption when comparing doses of
with 25 ml of H20 to doses with 250 to 500 ml. I also think he has done
some work on the temperature of the water and its effects on
bioavailability. I do not know the references for that work, so if someone
is familiar with it I would appreciate them.
Thanks
Art Straughn
UT Memphis
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Regarding the global recommendation "Take with a full glass of water" when
administering medications.
Response from Vahn A. Lewis, UTDB, 7/16/98
Peter Welling, while at the University of Wisconcin, School of Pharmacy
and his associates have been the principle sources of data in this area.
Quoting from his book(1):
"Although solid food tends to delay stomach emptying, liquids tend to speed
the process. In fact, increased fluid volume is th only known natural
stimulus to somach emptying. This stimulation results from activation of
strectch receptors in the stomach wall. When the fluid is water,
subsequent activation of the inhibitoruy receptors in the duodenum is
stopped, and the net result is rapid emptying of the stomach contents.
From a physical view point, drugs should be absorbed better from
concentrated solutions because of a greater concentration gradient.
However the reverse is often the case. Studies in experimental animals and
humans have shown that drug absorption from the GI tract increases when
drug is administered as a solid dosage form or as a solution, when the drug
is in a large fluid volume. The increased drug absorption results from the
combined effects of accelerated stomach emptying, rapid exposure of
dissolved drug molecules to a larger GI surface area, and faster
dissolution of the solid dosage forms."
FROM: Toothaker and Welling(6)
Fluid volume
Because the predominant driving force for the passive absorption of drugs
is the drug concentration gradient across the epithelial and capillary
membrane it wood appear axiomatic that drugs should be absorbed more
efficiently from concentrated solution than form dilute solutions.
However, in the intact animal or human, the reverse appears to be the case.
In animals, the toxicity of a large number of organic acids and bases, and
also inorganic ions, increased with the increasing compound dilution (17).
The absorption of both sodium pentobarbital and salicylate has also been
shown to be superior from dilute solution compared to concentrated solution
(18). Increased absorption of drugs when administered with large fluid
volumes compared to small fluid volumes in humans has also been
demonstrated (1)(ref. 5 below).
Several mechanisms have been proposed to explain increased
absorption from
dilute solutions. A concentrated drug solution may be sufficiently
hypertonic to delay stomach emptying, while a larger fluid volume present
in diluted drug solutions may stimulate stomach emptying due to the
activation of stomach tension receptors, thus presenting the drug to the
intestinal epithelial surface at a faster rate (18). A decreased solution
osmolarity has also been shown to cause increased absorption of both
ionized and un-ionized molecules from rat intestinal segments as a result
of an increase in the net mucosal to serosal solvent flux (19).
It is possible that for specific agents modification of the
recommendation to "take with a full glass of water" might be required.
However the material cited suggests that one should start with a
recommendation to take drugs with a full glass of water and then deal with
exceptions.
Most of the citations here are pretty old. I wonder if there is
some new
data in this area. I would still appreciate any updates.
I would also like to thank Dr, Diana Chow at the University of Houston
School of Pharmacy for the references from L. Shargel and A.B.C. Yu,
Applied Biopharmaceutics and Pharmacokinetics, Third ed. Appleton & Lange,
Norwalk, CT, 1993 pp129-130, 134. Note: the citation for the figure 7-13
on pp 129 was not included in the references or is mis-cited.
1. PG Welling, Pharmacokinetics, Processes and Mathematics, ACS Monograph
185, American Chemical Society, Washington DC, 1986. Pp27.
2. Koch PA, Schultz, CA, Wills, RJ, Hallquist SL, Welling PG, The
Influence of food and fluid ingestion on aspirin bioavailability. J. Pharm.
Sci. 67(11):1533-5, 1978.
3. Welling PG, Huang H, Koch PA, Craig WA, Madsen, PO, Bioavailability of
amoxicillin and amoxicillin in fasted and nonfasted subjects, 66(4):549-52,
1977.
4. Welling PG, Huang H, Hewitt, PF, Lyons, LL, Bioavailbility of
erythromycin stearate: influence of food and fluid volume. J. Pharm. Sci
67(6)764-6, 1978.
5. Welling PG, Influence of food and diet on gastrointestinal drug
absorbtion: A review. J. Pharmacokinet. Biopharm. 5:291-334, 1977.
6. Toothaker, RD and Welling PG, The effect of food on drug
bioavailability, Ann. Rev. Pharmacol. Toxicol. 1980, 20:173-99.
The following reference numbers follow the second quotation.
17. Ferguson, HC, Dilution of dose and oral toxicity. Toxicol. Appl.
Pharmacol, 19:164-68.
18. Borowitz, JL Moore, PF, Yim G, KW Miya, TS, Mechanism of enhanced drug
effects produced by dilution of the oral dose. Toxicol. Appl. Pharmacol.
19:164-68, 1971.
19. Ochsenfahrt H, Winne, D 1974. The contribution of solvent drag to the
intestinal absorption of the acidic drugs benzoic acid and salicylic acid
from the jejunum of the rat. Naunyn-Schmiedeberg's Arch. Pharmacol.
281:197-217, 1974.
I just found the following response and thank Art for it. I didn't find
anything on water temperature while I was searching but I only had a small
amount time to devote to it.
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